1. Field of the Invention
This invention relates to a microbial metabolite TAN-1511 and its related compounds, which are useful as therapeutic agents in the treatment of leukocytopenia resulting from various causes, such as diseases due to a decrease of leukocytes, or diseases requiring, from the therapeutic viewpoint, an increase of bone marrow cells or leukocytes.
2. Description of Related Art
In Hoppe-Seyler's Zeitschrift fur Physiologiche Chemie 364, pp 593-606 (1983), a synthetic peptide derived from lipoprotein produced by E. coli, which is shown by the formula: ##STR2## is disclosed.
And, in JPA H4(1992)-046194, WS 1279A substance shown by the formula: ##STR3## is disclosed.
Achiwa et al. synthesized these compounds as optical active compounds. [cf. JPA H4(1992)-099796, chem. Pharm. Bull. 39, p 2590 (1991) and Peptide Chemistry, p. 361 (1991)].
However, the compounds of this invention are not described in these references.
Incidentally, abbreviations of amino acid, peptide or the like used in the present invention are based on those in accordance with IUPAC-IUB Commission on Biochemical Nomenclature or those conventionally used in the relevant fields, and, possible optical isomers of amino acid are, unless otherwise specified, L-isomers.
Chemotherapy or radiotherapy of cancers causes serious leukocytopenia, which induces a lowering of resistance against infections or other various diseases so that sufficient therapeutic effects are not expected. This is being taken up as a grave concern in the field of cancer therapy. Under such circumstances, the development of drugs, which mitigate the suppression of hematopoietic function caused by these therapeutic methods and are capable of promoting the recovery of leukocyte number, has been ardently desired. And, in the therapy by bone marrow transplantation, drugs capable of promoting the proliferation of bone marrow cells then to be transplanted and capable of recovering the number of leukocyte promptly are desired.
While taking the present circumstances mentioned above into consideration, the present inventors pursued their studies, from a fresh viewpoint, on compounds having the action of increasing the number of leukocytes. As the result, the present inventors found that, among a great number of microbes isolated from soil, some microbes produce a novel substance, that these microbes belong to the genus Streptosporangium and that, by incubating these microbes in an appropriate culture medium, the compound capable of promoting the proliferation of bone marrow cells of mice and increasing the number of peripheral leukocyte can be accumulated in the culture medium. The present inventors then isolated this compound and, on the basis of its physico-chemical and biological properties, the compound was confirmed as a novel substance and called physiologically active substance TAN-1511 and named each component thereof TAN-1511A, B and C. And, since these compounds are respectively composed of different fatty acid moieties, the present inventors conducted also the study of synthesizing them as a single compound, respectively. Based on these findings, the present inventors made further studies to complete the present invention.